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Diagnosis and treatment
of genital herpes
The majority of people who develop genital herpes remain asymptomatic
and a general lack of understanding of the disease leads to unnecessary
morbidity, write Gerard Sheehan and Anthony Ryan
GENITAL HERPES REMAINS WORTHY OF ATTENTION despite
representing only 3% of all notifications to the National Disease Surveillance Centre.1 Evidence from new type specific
antibody tests shows that herpes simplex type 2 is common
and that only about a third of those infected are clinically
diagnosed.2
There are clear differences between physicians’ and
patients’ perceptions about the impact of genital herpes.
Some doctors may view genital herpes as a trivial, easy to
manage disease while failing to address the psychological
impact. Many patients view genital herpes as an entity with
a considerable stigma and embarrassment and tend to be
unaware of the impact of asymptomatic shedding.3,4
Some patients and doctors are unaware that oral sex is a
common route of transmission. Evidence suggests that most
transmission occurs from asymptomatic shedding of the
virus. The general lack of understanding hinders efforts to
control the spread of genital herpes and leads to unnecessary morbidity.5
Topical therapy has little clinical benefit and is not recommended6, while chronic suppressive therapy has clear
clinical efficacy but is underutilised and expensive.7
Atypical presentations of genital herpes are common and
may lead to misdiagnosis. These include epithelial abnormalities, such as fissures, furuncles, excoriations and
non-specific vulval erythema in women, and a linear fissure
of the prepuce and red spots on glans penis in men. Extragenital lesions can occur on the buttocks, groin and thighs,
and are commoner in women than men.3
In the future, more widespread availability of type specific
antibody tests may aid diagnosis. Perinatal transmission is
exceedingly rare but is the most serious complication of genital herpes. Genital herpes has also been shown to magnify
HIV transmission.
Natural history
Most cases are caused by herpes simplex virus type 2
(HSV-2) but many are due to herpes simplex virus type 1
(HSV-1), the usual cause of orolabial herpes. The mode of
infection is via contact with infected secretions on oral or
genital mucosal surfaces. With initial infection, HSV
ascends peripheral sensory nerves and enters sensory root
ganglia where latency is established and thus lifelong
infection.
Initial infection with either virus type is termed primary
infection and results in either symptomatic infection around
the site or asymptomatic and unrecognised disease. Primary
infection is often symptomatically severe and characterised
by widespread external and internal genital vesiculation,
ulceration and crusting followed by an array of systemic and
local symptoms and the patient is often febrile.
Pain, itching, dysuria, vaginal or urethral discharge and
tender inguinal adenopathy are the predominant local symptoms. The entire episode may take up to six weeks without
treatment and is often more prolonged and severe in
women.8
Complications may include aseptic meningitis and urinary
retention requiring catheterisation. Antivirals dramatically
shorten and diminish symptoms in primary genital herpes
compared to the more modest benefit derived from antiviral
treatment of recurrences.
In contrast to the long duration of the primary attack,
recurrences commonly last only a week and are rarely
accompanied by fever. Prodromal symptoms occur in 90%
of cases and range from a mild tingling sensation to shooting pains in the buttocks, legs and hips. These can occur
anything from one hour to several days prior to an episode.8
In 20% of episodes, lesions do not follow prodromal symptoms. Viral reactivation and clinical recurrences occur in
almost all patients who present with a clinically apparent
episode of genital herpes.7 Recurrence frequency in the genital area is much greater for HSV-2 than HSV-1 disease and
decreases with time.5 Women tend to have more severe
recurrences.9
Clinical diagnosis
Lesions of genital herpes are usually painful when touched
and this clinical sign helps differentiate from syphilis. Both
primary and recurrent HSV are accompanied by tender lymphadenopathy while non-tender nodes are more commonly
seen with syphilis.
Diagnosis can be made on clinical grounds if the patient
presents with the classical symptoms of recurrent painful
genital vesicles progressing to superficial ulceration.
Direct questioning about sexual practices such as homosexual contacts and contacts with commercial sex workers
may help differentiate genital herpes from rarer causes of
genital ulcers such as syphilis and chancroid.
Behcets syndrome should be considered as a differential
in those who have recurrent painful genital and oral ulcers,
often accompanied by urethritis, colitis, uveitis or stroke.
The syndrome is rare in Ireland but common in Asia,
especially Turkey.
Laboratory confirmation of herpes infection should be
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Sexual Health
sought in patients with atypical features, or where an alternative cause is possible.
Laboratory diagnosis
Viral culture provides definite diagnosis and can be
achieved in general practice. Negative tests can arise if
vesicular fluid is not swabbed or if the sample is sent when
the lesion is healing. Patients may need to be reassessed on
a number of occasions in order to make a definitive
diagnosis.
Type specific antibody testing is currently not routinely
available but may become available in the future. It may
have a role in specific situations such as confirming diagnosis in an asymptomatic partner, which would mean that
the issue of transmission risk would be irrelevant. In the
case of a pregnant woman with a partner with a history of
genital herpes, information from type specific antibodies
may help prevent primary infection in the crucial third
trimester. Non-specific antibody testing by complement fixation is of no clinical value due to the commonness of
HSV-1 in the community at large.
Subclinical shedding of virus
Much of the evidence concerning asymptomatic shedding
comes from an article in the New England Journal of Medicine.10 The clinical and virologic course of genital herpes
was studied prospectively in women who kept symptom
diaries and were instructed to provide daily samples from
the vulva, cervix and rectum for viral culture. Among women
with a history of HSV-2, subclinical shedding occurred on
2% of days with an average duration of 1.5 days.
HSV was isolated from several sites in the genital tract and
rectum. Half of the episodes of subclinical shedding
occurred within seven days of a clinical recurrence, while
the risk increased with the frequency of symptomatic recurrences. Subclinical shedding was also shown to be more
frequent among women with symptomatic recurrences compared to those with asymptomatic recurrences and it was
also found to be more frequent during the first year after a
clinical attack.10
Continuous suppressive aciclovir treatment (see Table 1)
reduces the number of days of subclinical viral shedding but
whether this leads to a reduction of sexual transmission is
not yet proven.11
Management of primary infection
Antivirals
All patients with primary infection should be considered
for antiviral therapy, as this has been shown to have a significant benefit in shortening the duration of symptoms.
Those who present within five days of the onset of an
episode or who have lesions still forming should certainly
have a course of one of the three available antiviral therapies (see Tables).They have equivalent efficacy in reducing
the severity and duration of an episode. The doses recommended are based on clinical studies and appear in The
Sanford Guide To Antimicrobial Therapy (31st Ed).12,13
A generic aciclovir is not available in Ireland but is available in the UK. Shorter courses of five to seven days
duration of valaciclovir or aciclovir may be efficacious, but
clinical studies have not been reported.
Supportive measures
Keep lesions dry and clean by washing two to three times
daily.14 Some experts suggest drying the genital area with a
44 FORUM November 2003
Table 1
Management of primary
infection
• Aciclovir 400mg tid for 10 days/
200mg five times daily for 10 days
• Famciclovir 250mg tid for 10 days
• Valaciclovir 100mg bid for 10 days
Table 2
Management of recurrent
genital herpes
• Aciclovir 400mg tid for 5 days
• Famciclovir 125mg bid for 5 days
• Valaciclovir 500mg bid for 5 days
hairdryer and using loosely fitting cotton underwear. Saline
baths and topical anaesthetic agents can be used as an
adjunct as well as appropriate analgesia
Counselling/prevention
Despite an incubation period ranging from two days to
three weeks, infection can be present without recognisable
signs in themselves or their partners. Recent development
of symptomatic vesicles does not necessarily imply infidelity.
Direct questioning about oral sex and a history of cold sores
in the partner may defuse a lot of unnecessary anxiety. Current partners may already have the virus without any
symptoms.
People who develop actual obvious symptoms are only the
tip of an iceberg, as the majority of cases remain asymptomatic. Reassurance should be given that there is no link
with cervical cancer or infertility and that the tendency for
attacks reduces with time.
One of the most difficult areas is discussing the diagnosis
with future partners. Parallels with oral herpes (using the
analogy of a cold sore on the genitals) may aid understanding. Simple advice on reducing the chance of transmission,
such as avoidance of sexual intercourse during symptoms or
in the prodromal period, should be reinforced.
have a role in prevention of transmission but they are by
no means 100% effective due to the possibility of extragenital sites of viral shedding.
Management of recurrent genital herpes
Patients should be encouraged to return for follow-up
appointments after their initial attack in order to avail of
episodic antiviral treatment. A diary of recurrences may be
useful to gauge whether chronic suppressive therapy is
indicated.
Episodic treatment of genital herpes has been shown to
be effective if started early in an attack and even then benefit is modest at best. If treatment is to be given, it should
be oral and early, if even modest benefit is to occur. This
may require the patient to have a back-up script or tablets
at home.
Oral aciclovir, famciclovir and valaciclovir (see Tables 1
and 2) have all been shown to be beneficial in reducing
symptoms by one to two days when used in an episodic fashion.4 We do not advocate the use of topical antivirals as they
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have little clinical benefit.12 The following table shows a cost
analysis with recommended doses based on clinical evidence.8,9
Indication for chronic suppression
Chronic suppressive therapy is safe and effective but
costly and under-utilised. It has been traditional practice to
wait at least 12 months to observe the frequency of recurrences before initiating chronic suppressive therapy.
Most trials of suppressive therapy have been done in
patients with a recurrence rate equivalent to or greater than
six per annum. It is likely, however, that patients with a
lower level of recurrence will also reduce their rate of
recurrence.
It is our practice to commence chronic suppression if
recurrences are having a substantial impact in terms of
physical symptoms or psychological strain. Experience with
suppressive therapy is most extensive with aciclovir where
safety and resistance data now extend to over 11 years of
continuous surveillance.
An option is to discontinue therapy after one year and
reassess recurrence frequency. However indefinite therapy
can be contemplated based on patients’ wishes. Short
courses of suppressive therapy may be helpful for some
patients in special circumstances (eg. exams). Chronic suppressive therapy is dispensed free of charge from STD
clinics.
Chronic suppressive therapy may reduce asymptomatic
shedding of genital herpes. In one study, 400mg of aciclovir
twice daily was shown to reduce viral shedding in women.7
Whether this translates into a public health benefit, due to
reduced transmission and a reduction in symptomatic cases,
has yet to be demonstrated.
Genital herpes in pregnancy
This is a rare disorder which can result in severe neurological impairment or death (there are about 10 cases per year in
the UK). Some 85% of cases of neonatal herpes result from
perinatal transmission of the virus during vaginal delivery.
This may be a result of symptomatic or asymptomatic shedding of the virus in the genital tract. The risks are greatest if
primary infection occurs in the third trimester and these
women should be considered for caesarean section.
Women with primary infection in the first or second trimester
should be considered for aciclovir. Current practice is to proceed to vaginal delivery unless lesions are present during
labour.5 Women with recurrences during pregnancy should be
reassured that these are usually brief and vaginal delivery is
appropriate if no lesions are present at labour.7
Key points
• Genital HSV is under-diagnosed and frequently misdiagnosed
• Up to 50% of genital herpes cases are attributable to HSV1 via oral sex
• Recurrences are commoner with HSV-2 compared to HSV1
• All primary herpes cases should be offered oral therapy
• Topical preparations should be avoided due to lack of efficacy
• Lesions may occur on thighs and buttocks
• Patients should be informed that they may have recurrences and that the virus can be shed in the absence of
symptoms.
• The main concern with pregnant women is acquisition of
primary herpes in the third trimester.
• Once recurrences are causing significant morbidity,
chronic suppressive therapy should be considered
• Genital herpes magnifies the transmission of HIV.
f
Gerard Sheehan is a consultant in infectious diseases and
director of the Mater Hospital STD Clinic, Anthony Ryan is a
GP at the Mater Hospital STD Clinic
References
1. National Disease Surveillance Centre. Quarterly Report on Sexually
Transmitted Infections, May 2001
2 Patel R, Cowan F, Barton S. Advising patients with genital herpes. BMJ
1997; 314:85
3 Corey Prof L, Simmons Dr A . Recommendations from the international
herpes management forum management strategies workshop 1997
4 Marchant J, Roe A. Genital herpes: Recognising and addressing patients’
needs.Herpes J 1997;4:36-41
5 Drake S et al. Improving the care of patients with genital herpes. BMJ 2000;
321:619-623
6. Corey et al. Double blind placebo controlled trial of topical aciclovir in first
and recurrent episodes of genital HSV.nejm1982;106,1313,1982
7. European Guidelines for the management of genital herpes. Patel R, Barton
S et al. Int J STD and AIDS 2001; 12 (suppl 3): 34-39
8 Gilbert, Moellering and Sande-The Sanford guide to antimicrobial therapy(31st ed) 2001: 101
9. 7 Corey L, Weld A. Sexually transmitted diseases (3rd ed): 285-308
10 Wald et al. Virologic characteristics of subclinical and symptomatic Genital
Herpes infections . NEJM 1999; 333: 770-775
11 Wald A et al.Supression of subclinical shedding of herpes simplex virus
type 2 with aciclovir. Ann. Intern Med 1996;124: 8-15
12. 8 Mindel A. Genital Herpes –The forgotten epidemic. Herpes; 1 (2): 39-48
13 Corey L, Weld A. Sexually transmitted diseases 3rd edition Ch.21 Pg 302
Table 21.3-Recommended regimens of antiviral chemotherapy for
mucocutaneous HSV Infection
14. Hunter Handsfield H. Colour atlas and synopsis of sexually transmitted
diseases (2nd§ Ed) 2001; 7
Irish College of General Practitioners
www.icgp.ie
46 FORUM November 2003